围产期干细胞库质量管理体系构建

围产期干细胞库质量管理体系（QMS）建设是保障干细胞产品和服务健康发展的基础工作。本文比较分析美国输血协会（AABB）、细胞疗法认证基金会（FACT）和ISO 9001的标准的架构、内容和侧重点,重点论述围产期干细胞库QMS构建的方法、步骤和参考模式。参照权威机构标准建立和运行QMS,能够保障我国围产期干细胞库标准化、规范化和科学化的建设和管理,提升我国干细胞库能力和信任水平。良好的QMS进一步促进干细胞与精准医疗战略性新兴产业升级,为建设健康中国提供动力。     

Optimization of defined medium for recombinant Komagataella phaffii expressing cyclodextrin glycosyltransferase

The cyclodextrin glycosyltransferase (CGTase) is an important enzyme for cyclodextrin (CD) production, and is also widely used in the biotechnology, food, and pharmaceuticals industries. Secretory CGTase production by recombinant Komagataella phaffii using defined medium is a promising approach because of low cost, less impurity protein. It was found that no CGTase was expressed using traditional defined medium (basal salt medium [BSM]) because of pH value decreasing significantly. CGTase was expressed by recombinant K. phaffii through pH maintenance in range of 5.5–7.0. β-CGTase activity increased to 122.0 U/mL after optimization of glycerol, phosphate buffer, pH value, ammonium sulfate, temperature, methanol, and additives based on BSM, establishing a modified defined medium. These results showed that it was necessary to establish recombinant K. phaffii-based special defined medium although the same host cell used for different heterologous protein expression.     

Efficient and green aqueous−solid system for transphosphatidylation to produce phosphatidylhydroxybutyrate: Potential drugs for central nervous system's diseases

The synthesis of nonnatural phospholipid, phosphatidylhydroxybutyrate (PB), was firstly introduced by phospholipase D (PLD)-mediated transphosphatidylation of phosphatidylcholine (PC) with sodium γ-hydroxybutyrate (NaGHB) in the aqueous–solid system. Nanoscale silicon dioxide (NSD) was employed as a carrier to provide an “artificial interphase” between PC and PLD. Special attention has been paid to the effect of the PC coverage on the surface area of hybrids of NSD-PC, the PC loading and the yield of PB. Results indicated that the highest PC loading of 98.3% and the highest PB yield of 97.3% were achieved. In addition, the free PLD in the aqueous–solid system showed the greater stability and pH tolerance than that in the traditional liquid–liquid system. The operational stability of free PLD solution was investigated. The yield of PB remained 70.7% after being used for five batches. The authors provide a new idea for drug design and the potential source of PB for medical experiments. PB is a potential drug and may have the excellent performance in the treatment of central nervous system's diseases. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2726, 2019     

Advancements in endometrial epithelial stem cell research

Science China Life Sciences -     

LncDACH1 promotes mitochondrial oxidative stress of cardiomyocytes by interacting with sirtuin3 and aggravates diabetic cardiomyopathy

Science China Life Sciences - Diabetic cardiomyopathy (DCM) is a common complication in diabetic patients. The molecular mechanisms of DCM remain to be fully elucidated. The intronic long noncoding...     

Melatonin inhibits Gram-negative pathogens by targeting citrate synthase

Bacterial infections caused by Gram-negative pathogens represent a growing burden for public health worldwide. Despite the urgent need for new antibiotics that effectively fight against pathogenic bacteria, very few compounds are currently under development or approved in the clinical setting. Repurposing compounds for other uses offers a productive strategy for the development of new antibiotics. Here we report that the multifaceted melatonin effectively improves survival rates of mice and decreases bacterial loads in the lung during infection. Mechanistically, melatonin specifically inhibits the activity of citrate synthase of Gram-negative pathogens through directly binding to the R300, D363, and H265 sites, particularly for the notorious Pasteurella multocida. These findings highlight that usage of melatonin is a feasible and alternative therapy to tackle the increasing threat of Gram-negative pathogen infections via disrupting metabolic flux of bacteria.

     

Cryo-EM structures reveal the dynamic transformation of human alpha-2-macroglobulin working as a protease inhibitor

Science China Life Sciences - Human alpha-2-macroglobulin is a well-known inhibitor of a broad spectrum of proteases and plays important roles in immunity, inflammation, and infections. Here, we...     

Engineering Saccharomyces cerevisiae-based biosensors for copper detection

Heavy metals, that is Cu(II), are harmful to the environment. There is an increasing demand to develop inexpensive detection methods for heavy metals. Here, we developed a yeast biosensor with reduced-noise and improved signal output for potential on-site copper ion detection. The copper-sensing circuit was achieved by employing a secondary genetic layer to control the galactose-inducible (GAL) system in Saccharomyces cerevisiae. The reciprocal control of the Gal4 activator and Gal80 repressor under copper-responsive promoters resulted in a low-noise and sensitive yeast biosensor for copper ion detection. Furthermore, we developed a betaxanthin-based colorimetric assay, as well as 2-phenylethanol and styrene-based olfactory outputs for the copper ion detection. Notably, our engineered yeast sensor confers a narrow range switch-like behaviour, which can give a ‘yes/no’ response when coupled with a betaxanthin-based visual phenotype. Taken together, we envision that the design principle established here might be applicable to develop other sensing systems for various chemical detections.